Peters L L, Birkenmeier C S, Bronson R T, White R A, Lux S E, Otto E, Bennett V, Higgins A, Barker J E
Jackson Laboratory, Bar Harbor, Maine 04609.
J Cell Biol. 1991 Sep;114(6):1233-41. doi: 10.1083/jcb.114.6.1233.
Mice homozygous for the nb mutation (Chromosome 8) have a severe hemolytic anemia and develop a psychomotor disorder at 6 mo of age. The nb/nb mice are deficient in erythroid ankyrin (Ank-1) but, until the present study, the role of Ank-1 and of Ank-2 (brain ankyrin) in disease genesis was unknown. In normal erythroid tissues, we show that two major transcripts are expressed from Ank-1, and one of these is also present at high levels in the cerebellum. By in situ hybridization and immunocytochemistry, Ank-1 localizes to the cerebellar Purkinje cells and, to a lesser extent, the granule cells. In nb/nb mice, Ank-1 transcripts are markedly reduced in both erythroid and neural tissue, and nb/nb Purkinje cells and granule cells are nearly devoid of Ank-1. The neurological syndrome appears concurrently with a dramatic loss of Purkinje cells. Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear.
nb 突变（位于 8 号染色体）的纯合子小鼠患有严重的溶血性贫血，并在 6 月龄时出现精神运动障碍。nb/nb 小鼠缺乏红细胞锚蛋白（Ank-1），但在本研究之前，Ank-1 和 Ank-2（脑锚蛋白）在疾病发生中的作用尚不清楚。在正常的红细胞组织中，我们发现 Ank-1 表达两种主要转录本，其中一种在小脑中也高水平存在。通过原位杂交和免疫细胞化学方法，Ank-1 定位于小脑浦肯野细胞，在颗粒细胞中的定位程度较低。在 nb/nb 小鼠中，Ank-1 转录本在红细胞和神经组织中均显著减少，nb/nb 浦肯野细胞和颗粒细胞几乎没有 Ank-1。神经综合征与浦肯野细胞的急剧丢失同时出现。Ank-2 定位于 3 号染色体，其表达不受 nb 突变的影响。我们得出结论，Ank-1 是浦肯野细胞稳定性所特需的，缺乏 Ank-1 时，会出现浦肯野细胞丢失和神经症状。
